Adenosine receptors and behavioral actions of methylxanthines [caffeine/theophylline/N 6-cyclohexyladenosine/N 6-(phenylisopropyl)adenosine]

Solomon H Snyder, J. J. Katims, Z. Annau, R. F. Bruns, J. W. Daly

Research output: Contribution to journalArticle

Abstract

Central stimulant actions of 10 methylxanthines in mice correlate with affinities for adenosine receptors labeled with N 6 -[ 3H]cyclohexyladenosine. Affinities of methylxanthines for adenosine receptors are consonant with central levels attained at behaviorally effective doses. The much higher concentrations of methylxanthines required to influence benzodiazepine receptor binding do not correlate with behavioral potency. N 6-(L-Phenyl-isopropyl)adenosine (L-PIA), a metabolically stable analog of adenosine with high affinity for adenosine receptors, is an extremely potent behavioral depressant, reducing locomotor activity of mice at doses as little as 0.05 μmol/kg. The D isomer, which has much less affinity for adenosine receptors, is much less active as a central depressant. Theophylline stimulates locomotor activity and reverses depressant effects of L-PIA. Caffeine or 1,7-dimethylxanthine, when administered alone, elicits biphasic effects, with locomotor depression at lower doses and stimulation at higher doses. When administered with L-PIA, even low doses of caffeine produce marked stimulation. 3-Isobutyl-1-methylxanthine given alone elicits only behavioral depression. However, like theophylline and caffeine, isobutylmethylxanthine reverses the L-PIA-evoked depression, converting it into pronounced locomotor stimulation. The data strongly suggest that the behavioral stimulant effects of methylxanthines involve a blockade of central adenosine receptors.

Original languageEnglish (US)
Pages (from-to)3260-3264
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume78
Issue number5 I
DOIs
StatePublished - 1981

Fingerprint

Phenylisopropyladenosine
Purinergic P1 Receptors
Theophylline
Caffeine
Adenosine
Locomotion
Central Nervous System Stimulants
1-Methyl-3-isobutylxanthine
GABA-A Receptors
methylxanthine
N(6)-cyclohexyladenosine

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

@article{5e15208cbda941b8940c64e27d0e5000,
title = "Adenosine receptors and behavioral actions of methylxanthines [caffeine/theophylline/N 6-cyclohexyladenosine/N 6-(phenylisopropyl)adenosine]",
abstract = "Central stimulant actions of 10 methylxanthines in mice correlate with affinities for adenosine receptors labeled with N 6 -[ 3H]cyclohexyladenosine. Affinities of methylxanthines for adenosine receptors are consonant with central levels attained at behaviorally effective doses. The much higher concentrations of methylxanthines required to influence benzodiazepine receptor binding do not correlate with behavioral potency. N 6-(L-Phenyl-isopropyl)adenosine (L-PIA), a metabolically stable analog of adenosine with high affinity for adenosine receptors, is an extremely potent behavioral depressant, reducing locomotor activity of mice at doses as little as 0.05 μmol/kg. The D isomer, which has much less affinity for adenosine receptors, is much less active as a central depressant. Theophylline stimulates locomotor activity and reverses depressant effects of L-PIA. Caffeine or 1,7-dimethylxanthine, when administered alone, elicits biphasic effects, with locomotor depression at lower doses and stimulation at higher doses. When administered with L-PIA, even low doses of caffeine produce marked stimulation. 3-Isobutyl-1-methylxanthine given alone elicits only behavioral depression. However, like theophylline and caffeine, isobutylmethylxanthine reverses the L-PIA-evoked depression, converting it into pronounced locomotor stimulation. The data strongly suggest that the behavioral stimulant effects of methylxanthines involve a blockade of central adenosine receptors.",
author = "Snyder, {Solomon H} and Katims, {J. J.} and Z. Annau and Bruns, {R. F.} and Daly, {J. W.}",
year = "1981",
doi = "10.1073/pnas.78.5.3260",
language = "English (US)",
volume = "78",
pages = "3260--3264",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "5 I",

}

TY - JOUR

T1 - Adenosine receptors and behavioral actions of methylxanthines [caffeine/theophylline/N 6-cyclohexyladenosine/N 6-(phenylisopropyl)adenosine]

AU - Snyder, Solomon H

AU - Katims, J. J.

AU - Annau, Z.

AU - Bruns, R. F.

AU - Daly, J. W.

PY - 1981

Y1 - 1981

N2 - Central stimulant actions of 10 methylxanthines in mice correlate with affinities for adenosine receptors labeled with N 6 -[ 3H]cyclohexyladenosine. Affinities of methylxanthines for adenosine receptors are consonant with central levels attained at behaviorally effective doses. The much higher concentrations of methylxanthines required to influence benzodiazepine receptor binding do not correlate with behavioral potency. N 6-(L-Phenyl-isopropyl)adenosine (L-PIA), a metabolically stable analog of adenosine with high affinity for adenosine receptors, is an extremely potent behavioral depressant, reducing locomotor activity of mice at doses as little as 0.05 μmol/kg. The D isomer, which has much less affinity for adenosine receptors, is much less active as a central depressant. Theophylline stimulates locomotor activity and reverses depressant effects of L-PIA. Caffeine or 1,7-dimethylxanthine, when administered alone, elicits biphasic effects, with locomotor depression at lower doses and stimulation at higher doses. When administered with L-PIA, even low doses of caffeine produce marked stimulation. 3-Isobutyl-1-methylxanthine given alone elicits only behavioral depression. However, like theophylline and caffeine, isobutylmethylxanthine reverses the L-PIA-evoked depression, converting it into pronounced locomotor stimulation. The data strongly suggest that the behavioral stimulant effects of methylxanthines involve a blockade of central adenosine receptors.

AB - Central stimulant actions of 10 methylxanthines in mice correlate with affinities for adenosine receptors labeled with N 6 -[ 3H]cyclohexyladenosine. Affinities of methylxanthines for adenosine receptors are consonant with central levels attained at behaviorally effective doses. The much higher concentrations of methylxanthines required to influence benzodiazepine receptor binding do not correlate with behavioral potency. N 6-(L-Phenyl-isopropyl)adenosine (L-PIA), a metabolically stable analog of adenosine with high affinity for adenosine receptors, is an extremely potent behavioral depressant, reducing locomotor activity of mice at doses as little as 0.05 μmol/kg. The D isomer, which has much less affinity for adenosine receptors, is much less active as a central depressant. Theophylline stimulates locomotor activity and reverses depressant effects of L-PIA. Caffeine or 1,7-dimethylxanthine, when administered alone, elicits biphasic effects, with locomotor depression at lower doses and stimulation at higher doses. When administered with L-PIA, even low doses of caffeine produce marked stimulation. 3-Isobutyl-1-methylxanthine given alone elicits only behavioral depression. However, like theophylline and caffeine, isobutylmethylxanthine reverses the L-PIA-evoked depression, converting it into pronounced locomotor stimulation. The data strongly suggest that the behavioral stimulant effects of methylxanthines involve a blockade of central adenosine receptors.

UR - http://www.scopus.com/inward/record.url?scp=0001441518&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0001441518&partnerID=8YFLogxK

U2 - 10.1073/pnas.78.5.3260

DO - 10.1073/pnas.78.5.3260

M3 - Article

C2 - 6265942

AN - SCOPUS:0001441518

VL - 78

SP - 3260

EP - 3264

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 5 I

ER -